Community-acquired methicillin-resistant

Autophagy, a major bulk proteolytic pathway, contributes to intracellular protein turnover, together with protein synthesis. Both are subject to dynamic control by amino acids and insulin. The mechanisms of signaling and cross-talk of their physiological anabolic effects remain elusive. Recent studies established that amino acids and insulin induce p70 S6 kinase (p70 S6k ) phosphorylation by mTOR, involved in translational control of protein synthesis. Here, the signaling mechanisms of amino acids and insulin in macroautophagy in relation to mTOR were investigated. In isolated rat hepatocytes, both regulatory amino acids (RegAA) and insulin coordinately activated p70 S6k phosphorylation, which was completely blocked by rapamycin, an mTOR inhibitor. However, rapamycin blocked proteolytic suppression by insulin, but did not block inhibition by RegAA. These contrasting results suggest that insulin controls autophagy through the mTOR pathway, but amino acids do not. Furthermore, micropermeabilization with Saccharomyces aureus ␣-toxin completely deprived hepatocytes of proteolytic responsiveness to RegAA and insulin, but still maintained p70 S6k phosphorylation by RegAA. In contrast, Leu 8 -MAP, a non-transportable leucine analogue, did not mimic the effect of leucine on p70 S6k phosphorylation, but maintained the activity on proteolysis. Finally, BCH, a System L-specific amino acid, did not affect proteolytic suppression or mTOR activation by leucine. All the results indicate that mTOR is not common to the signaling mechanisms of amino acids and insulin in autophagy, and that the amino acid signaling starts extracellularly with their "receptor(s)," probably other than transporters, and is mediated through a novel route distinct from the mTOR pathway employed by insulin.

Compliance with therapy is the single most important factor in Helicobacter pylori (H. pylori) eradication. Poorer levels of compliance with therapy are associated with significantly lower levels of eradication. Numerous factors can contribute to achieving good levels of compliance. These include the complexity and duration of treatment. It is also important that the physician is motivated to ensure eradication is confirmed and the patient is sufficiently informed to empower him or her to achieve high levels of compliance. Compliance is also contingent on medication regimes that are simple, safe, tolerable and efficacious. The opportunity to improve compliance exists at every point of contact between the patient and the medical services. Experts and opinion leaders in the field can play a role by ensuring that physicians are educated and motivated enough to encourage and support compliance with H. pylori eradication therapy. Both patients and physicians need to be aware of the importance of the bacterium in causing disease. The importance of the doctorpatient relationship is paramount. Pragmatic strategies that may be of assistance may come in the form of polypills, combined Blister Packs, adjuvant therapies and modified release compounds. Colleagues such as pharmacists and nurse specialists can also play an important role and should be actively engaged. Structured aftercare and follow up offers the best chance for ensuring compliance and subsequent eradication of the H. pylori pathogen.

No abstract