Diagnostic criteria for autoimmune hepatitis: What is the gold standard?
✍ Scribed by Rajan Kochar; Michael Fallon
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 56 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
quence of the MPT. Similarly, minocycline (20 M) inhibited mitochondrial TMRM release and calcein uptake even after longer times of reperfusion, demonstrating directly that minocycline blocks the characteristic inner membrane permeabilization of the MPT (Fig. 1C). Thus, minocycline protects against mitochondrial dysfunction after both warm and cold ischemia-reperfusion by prevention of the MPT. These results under truly physiological conditions are simply incompatible with the proposal that the chief effects of minocycline are respiratory inhibition and MPT promotion. Rather, such mitochondrial dysfunction is likely the basis for loss of efficacy at higher nontherapeutic minocycline concentrations. Currently, we are screening a panel of tetracycline derivatives for compounds with a larger therapeutic window of efficacy.
Minocycline is a well-characterized and cost-effective anitbiotic of proven safety in a broad spectrum of indications. 6 In rare instances, hepatotoxicity after chronic use occurs, which is attributed to the metabolite 4-epiminocycline. 7 However, such toxicity would be unlikely after one-time use to minimize storage-reperfusion injury to transplanted livers. To decrease infection, antibiotics are a standard peritransplant regimen, and use of minocycline in donors, recipients, and during graft storage might have added benefit, especially in marginal livers from higher risk donors or in livers subjected to longer periods of storage. Overall, we agree with Månsson et al. that the safety and efficacy of minocycline for use in clinical liver transplantation deserve further exploration.