Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation

Literacy and blood pressure – do healthcare systems influence this relationship? A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Limited literacy is common among patients with chronic conditions and is associated with poor health outcomes. We sought to determine the association between literacy and blood pressure in primary care patients with hypertension and to determine if this relationship was consistent across distinct systems of healthcare delivery.</p> <p>Methods</p> <p>We conducted a cross-sectional study of 1224 patients with hypertension utilizing baseline data from two separate, but similar randomized controlled trials. Patients were enrolled from primary care clinics in the Veterans Affairs healthcare system (VAHS) and a university healthcare system (UHS) in Durham, North Carolina. We compared the association between literacy and the primary outcome systolic blood pressure (SBP) and secondary outcomes of diastolic blood pressure (DBP) and blood pressure (BP) control across the two different healthcare systems.</p> <p>Results</p> <p>Patients who read below a 9^thgrade level comprised 38.4% of patients in the VAHS and 27.5% of the patients in the UHS. There was a significant interaction between literacy and healthcare system for SBP. In adjusted analyses, SBP for patients with limited literacy was 1.2 mmHg lower than patients with adequate literacy in the VAHS (95% CI, -4.8 to 2.3), but 6.1 mmHg higher than patients with adequate literacy in the UHS (95% CI, 2.1 to 10.1); (p = 0.003 for test of interaction). This literacy by healthcare system interaction was not statistically significant for DBP or BP control.</p> <p>Conclusion</p> <p>The relationship between patient literacy and systolic blood pressure varied significantly across different models of healthcare delivery. The attributes of the healthcare delivery system may influence the relationship between literacy and health outcomes.</p

Perspectives on a ‘Sit Less, Move More’ Intervention in Australian Emergency Call Centres

Background: Prolonged sitting is associated with increased risk of chronic diseases. Workplace programs that aim to reduce sitting time (sit less) and increase physical activity (move more) have targeted desk-based workers in corporate and university settings with promising results. However, little is known about 'move more, sit less' programs for workers in other types of jobs and industries, such as shift workers. This formative research examines the perceptions of a 'sit less, move more' program in an Australian Emergency Call Centre that operates 24 hours per day, 7 days per week.  Methods: Participants were employees (N = 39, 72% female, 50% aged 36-55 years) recruited from Emergency Services control centres located in New South Wales, Australia. The 'sit less, move more' intervention, consisting of emails, posters and timer lights, was co-designed with the management team and tailored to the control centre environment and work practices, which already included electronic height-adjustable sit-stand workstations for all call centre staff. Participants reported their perceptions and experiences of the intervention in a self-report online questionnaire, and directly to the research team during regular site visits. Questionnaire topics included barriers and facilitators to standing while working, mental wellbeing, effects on work performance, and workplace satisfaction. Field notes and open-ended response data were analysed in an iterative process during and after data collection to identify the main themes.  Results: Whilst participants already had sit-stand workstations, use of the desks in the standing position varied and sometimes were contrary to expectations (e.g, less tired standing than sitting; standing when experiencing high call stress). Participants emphasised the "challenging" and "unrelenting" nature of their work. They reported sleep issues ("always tired"), work stress ("non-stop demands"), and feeling mentally and physically drained due to shift work and length of shifts. Overall, participants liked the initiative but acknowledged that their predominantly sitting habits were entrenched and work demands took precedence.  Conclusions: This study demonstrates the low acceptability of a 'sit less, move more' program in shift workers in high stress environments like emergency call centres. Work demands take priority and other health concerns, like poor sleep and high stress, may be more salient than the need to sit less and move more during work shifts

Defective Interfering Viral Particles in Acute Dengue Infections

While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3′ and 5′ ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6–36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses

Evidence for a Prepore Stage in the Action of Clostridium perfringens Epsilon Toxin

Clostridium perfringens epsilon toxin (ETX) rapidly kills MDCK II cells at 37°C, but not 4°C. The current study shows that, in MDCK II cells, ETX binds and forms an oligomeric complex equally well at 37°C and 4°C but only forms a pore at 37°C. However, the complex formed in MDCK cells treated with ETX at 4°C has the potential to form an active pore, since shifting those cells to 37°C results in rapid cytotoxicity. Those results suggested that the block in pore formation at 4°C involves temperature-related trapping of ETX in a prepore intermediate on the MDCK II cell plasma membrane surface. Evidence supporting this hypothesis was obtained when the ETX complex in MDCK II cells was shown to be more susceptible to pronase degradation when formed at 4°C vs. 37°C; this result is consistent with ETX complex formed at 4°C remaining present in an exposed prepore on the membrane surface, while the ETX prepore complex formed at 37°C is unaccessible to pronase because it has inserted into the plasma membrane to form an active pore. In addition, the ETX complex rapidly dissociated from MDCK II cells at 4°C, but not 37°C; this result is consistent with the ETX complex being resistant to dissociation at 37°C because it has inserted into membranes, while the ETX prepore readily dissociates from cells at 4°C because it remains on the membrane surface. These results support the identification of a prepore stage in ETX action and suggest a revised model for ETX cytotoxicity, i) ETX binds to an unidentified receptor, ii) ETX oligomerizes into a prepore on the membrane surface, and iii) the prepore inserts into membranes, in a temperature-sensitive manner, to form an active pore

Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice

Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS) induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1β, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress. © 2012 Brass et al