Pro-active strategies

Accident and ill-health reporting, recording and investigation provide feedback as to the indirect and direct causes of accidents. The study of past accident causes provides information for the development of future pro-active strategies. The limitations of accident data as a measure of safety performance are covered in Chapter 4 - Safety Management Systems. 

Any management system should be of a mainly pro-active nature, concerned with the prevention of accidents and ill-health, control of the working environment and the various factors affecting that environment. However, there will always be a place for the various reactive strategies as a means of obtaining feedback on performance. 

The Colombian authorities have been pro-active and civil society has been very vocal in protecting and assisting IDPs. In 1997 a Law on internal displacement was enacted, adopting measures for the prevention of forced displacement and for the assistance, protection, socio-economic consolidatioii, and stabilization of persons internally displaced by violence. Its implementation, however, was rather limited due to the lack of a comprehensive strategy to address internal displacement, which should include, inter alia, the integration of the issue of displacement into the peace process. 

The danger of epimerization during the coupling of segments exists for all cases, except when me activated residue is Pro and Gly, with a few exceptions (see Section 7.23). The obvious is to design a strategy mat involves activation at these residues only. Options to try to minimize me side reaction for activation at other residues are as follows ... 

Importantly, knowledge of intestinal bile acid transport and metabolism, coupled with increased understanding of the mechanistic basis of the pro-tumorigenic activity of bile acids against CRC cells in vitro, has recently led to development and testing of bile acid-based treatment and prevention strategies for sporadic and inflammatory bowel-disease-associated CRC. Existing evidence that manipulation of the luminal secondary bile acid pool and/or therapy with ursodeoxycholic acid (UDCA) may have promise for prevention of CRC will be assessed. 

Figure 5.2 Therapeutic interventions for decreasing colorectal mucosal bile acid exposure as a CRC chemoprevention strategy. 1) Lifestyle modifications including reduction in dietary animal fat and increased fibre intake may, at least partly, be explained by reduction in luminal primary (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary (deoxycholic acid [DCA] and lithocholic acid [LCA]) bile acids. 2) Reduction of secondary bile acids, which are believed to have pro-carcinogenic activity could be obtained by decreased bacterial conversion from primary bile acids. 3) Alternatively, bile acids could be sequestered by chemical binding agents, e.g. aluminium hydroxide (Al(OH)3) or probiotic bacteria. 4) Exogenous ursodeoxycholic acid (UDCA) can reduce the luminal proportion of secondary bile acids and also has direct anti-neoplastic activity on colonocytes in vitro.

ADEPT strategies have been described but only the carboxypeptidase G2 approach has been tested in patients so far. In a phase I clinical trial, patients with non-resectable metastatic or locally recurrent colorectal carcinoma were treated with ADEPT. Carboxypeptidase G2 activity was found in metastatic tumour biopsies. The pro-drug was converted into the active drug but leakage into the bloodstream also occurred [22,144]. 

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