Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Age-related bone loss eventually leads to osteopenia in men and women. The etiology of age-related bone loss is currently unknown; however, decreased osteoblast activity contributes to this phenomenon. In turn, osteoblast proliferation and function is dependent on energy production, thus the loss of energy production that occurs with age may account for the deficient osteoblast activity. Carnitine and dehydroepiandrosterone-sulfate (DHEAS), both of which decline with age, promote energy production through fatty acid metabolism. Thus, we hypothesized that carnitine and DHEAS would increase osteoblast activity in vitro . Accordingly, we measured the effect of carnitine and DHEAS on palmitic acid oxidation as a measure of energy production, and alkaline phosphatase (ALP) activity and collagen type I (COL) as indices of osteoblast function in primary porcine osteoblast-like cell cultures. Carnitine (10 −3 and 10 −1 M) but not DHEAS (10 −9 , 10 −8 , and 10 −7 M) increased carnitine levels within the cells. Carnitine alone and in combination with DHEAS increased palmitic acid oxidation. Both carnitine and DHEAS alone and in an additive fashion increased ALP activity and COL levels. These results demonstrate that in osteoblast-like cells in vitro, energy production can be increased by carnitine and osteoblast protein production can be increased by both carnitine and DHEAS. These data suggest that carnitine and DHEAS supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42359/1/223-64-6-527_64n6p527.pd

Systematic review of influenza resistance to the neuraminidase inhibitors

<p>Abstract</p> <p>Background</p> <p>Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu^®) and zanamivir (Relenza^®); and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review.</p> <p>The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms.</p> <p>Results</p> <p>We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%). The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral resistance among subjects given peramivir and was reported to be 0%. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. A meta-analysis of 4 studies reporting association between oseltamivir-resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Oseltamivir-resistance was not statistically significantly associated with other clinical complications and symptoms.</p> <p>Conclusion</p> <p>Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance may be significantly associated with pneumonia. In contrast, zanamivir resistance has been rarely reported to date.</p

An integrated graphic data display improves detection and identification of critical events during anesthesia.

OBJECTIVE: To show that an integrated graphic data display can shorten the time taken to detect and correctly identify critical events during anesthesia. METHODS: We developed a graphic display which presents 30 anesthesia-related physiologic variables as shapes and colors, rather than traditional digits and waveforms. To evaluate the new display, we produced four critical events on a computer-based anesthesia simulator and asked two groups of five anesthesiologists to identify the events as quickly as possible. One group observed the new display while the other group viewed a traditional cardiovascular monitor with digital and waveform displays. RESULTS: The group which observed the integrated graphic display saw changes caused by inadequate paralysis 2.4 min sooner, and changes caused by a cuff leak 3.1 min sooner than those observing the traditional display. The integrated display group correctly identified the reason for the change 2.8 min sooner for inadequate paralysis, 3.1 min sooner for cuff leak and 3.1 min sooner for bleeding. These differences were all statistically significant. CONCLUSIONS: The results show that some simulated critical events are detected and correctly identified sooner, when an anesthesiologist views an integrated graphic display, rather than a traditional digital/waveform monitor

Educational simulation of the electroencephalogram (EEG)

We describe a model for simulating a spontaneous electroencephalogram (EEG) and for simulating the effects of anesthesia on the EEG, to allow anesthesiologists and EEG technicians to learn and practice intraoperative EEG monitoring. For this purpose, we developed a linear model to manipulate the amplitude of the activity in each of the traditional EEG frequency bands. Burst suppression patterns are simulated by manipulating an overall gain. To demonstrate the model feasibility, model parameters for thiopental and isoflurane were estimated guided by published data on the EEG effects of these anesthetic drugs. Using these estimates, EEG time signals were simulated for isoflurane at various partial pressures, and for bolus intravenous doses of thiopental. Comparison with actual recorded EEG signals showed that the changes produced by isoflurane and thiopental in the simulated signals are very similar to the changes in the actual signals, which was confirmed by two clinicians with experience and routine practice in intraoperative EEG monitoring