Self-acid-dosing

Insulin Lispro was the first recombinant fast-acting insulin analogue to gain marketing approval (Table 8.3). It displays an amino acid sequence identical to native human insulin, with one alteration — an inversion of the natural proline lysine sequence found at positions 28 and 29 of the insulin jS-chain. This simple alteration significantly decreased the propensity of individual insulin molecules to self-associate when stored at therapeutic dose concentrations. The dimerization constant for Insulin Lispro is 300 times lower than that exhibited by unmodified human insulin. Structurally, this appears to occur as the change in sequence disrupts the formation of inter-chain hydrophobic interactions critical to self-association. 

Modified-release formulations of nicotinic acid do not appear to be better tolerated than regular formulations, flushing and itching being the most common adverse effects (SEDA-19, 206). There have also been several reports of hepatotoxicity with this form of the drug (SEDA-16,438). Other adverse effects are hepatotoxicity (apparently a dose-related direct toxic effect), hyperglycemia, and hyperuricemia. It has been questioned whether the modified-release formulation, which is available over the counter in some countries, ought to continue to be available for self-medication in view of its serious adverse effects (2,3). 

An aspect of life in clouds that is beyond the scope of this book (cold environments) is potential life in Venusian clouds. The surface of Venus is too hot (464°C) for liquid water or carbon-based life (Cockell 1999). Atmospheric constraints include sulfuric acid clouds and high doses of ultraviolet radiation in principle, these atmospheric constraints can be overcome (Cockell 1999 Schulze-Makuch et al. 2004), which means that Venus could be close to possessing a habitable environment. However, it still remains to be demonstrated that the residence time in Venusian clouds is sufficiently long to create a self-sustaining ecosystem. 

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