Pancreas substitution

Use Anal aim of exocrine pancreas substitution therapy is to eliminate malabsorption and to maintain adequate nutrition. Treatment of exocrine insufficiency of the pancreas ought to be easily achieved by administering an extract of mammalian (e.g., porcine) pancreas. Unfortunately, successful treatment is sometimes not easy to achieve and elimination of malabsorption can be difficult to maintain, notwithstanding the availability of potent porcine pancreatic extracts. Problems inherent in these pancreatin preparations themselves, like particularities in the environment in which the enzymes are expected to work, must also be considered. 

Four major enzyme groups are secreted lipolytic, proteolytic, amylolytic, and nucleic acid splitting enzymes. These pancreatic enzymes, some of which are secreted in multiple forms, possess specificities complementary to the intestinal membrane-bound enzymes (Table 1). Fresh, uncontaminated pancreatic juice is without proteolytic activity because these enzymes are in the form of inactive zymogens. An important fraction of the calcium in pancreatic juice accompanies the enzymes, especially a-amylase. Human pancreatic juice is most close to that of the pig, with high proportions of lipase and a-amylase in comparison with other mammals [1]. Therefore, pig pancreas extract, pancreatin, has up to now been the preferred enzyme source for therapeutic pancreas substitution. 

Various cyclic esters have been subjected to hpase-catalyzed ring-opening polymerization. Lipase catalyzed the ring-opening polymerization of 4- to 17-membered non-substituted lactones.In 1993, it was first demonstrated that medium-size lactones, 8-valerolactone (8-VL, six-membered) and e-caprolactone (e-CL, seven-membered), were polymerized by lipases derived from Candida cylindracea, Burkholderia cepacia (lipase BC), Pseudomonas fluorescens (lipase PF), and porcine pancreas (PPL). °... 

In the biomedical area, SPHs and SPH composites can be used to make various biomedical devices, such as artificial pancreas, artificial cornea, and artihcial skin, articular cartilage, soft tissue substitutes, cell growth substrates in tissue engineering, burn dressings, surgical augmentation of the female breast, or hemoperfusion in blood detoxification and in the treatment of uremia. 

In Type-I diabetes, which is due to the loss of insulin-producing cells as a consequence of autoimmune disorders, substitution of insulin is the most important measure. However, merely to inject one daily dose is not an adequate therapy. Here, the objective is to mimic the daily variations in plasma insulin which are closely related to food intake. One such attempt which has improved microvascular complications is intensified insulino-therapy through multiple daily injections of insulin. Another approach is to develop techniques of islet transplantation and using a bioartificial pancreas. In the case of islet transplantation, tissues will not only respond to changes in blood glucose levels but also to hormones of the entero-insular axis. 

Group-selective and enantioselective hydrolyses as well as the influence of the alkyl group of the acyl function and the cosolvent upon the enantioselectivity are demonstrated by the pig pancreas lipase-catalyzed hydrolysis of the methoxycarbonyl substituted diacylated propanediol corresponding to the monoesters 18. 

A series of alkyl, alkoxy or acylamino 1,3-proanediol derivatives substituted in 2-position have been subjected to lipase-catalyzed acylation, and the monoacetates (1-12, 19, 20, 23-38, 40-42) were obtained with moderate to high enantiomeric excess (Table 11.1-17). For the monoacetates 1-12, reactions with and in ethyl acetate are usually slower than those with and in vinyl acetate. As in the hydrolysis of the corresponding diacetates, much higher selectivities were recorded with the yet unidentified carboxyl esterase from crude pig pancreas lipase. An excellent lipase for the enantioselective acylation of 3-benzyloxy-l,3-propane diol is Pseudomonas fluor-escens lipase, which gives high selectivity with vinyl acetate, isopropenyl acetate and ethyl acetate. By carrying the acylation further, to a certain extent to the diacetate, the enantiomerically pure monoacetate should be obtainable. 

As well as the above-described intermolecular alcoholysis of esters, the intramolecular version has been successfully utilized for the synthesis of lactones from racemic hydroxy carboxylic acid esters (25-41, 64—66) (Table 11.1-22). High selectivity in the pig pancreas lipase-catalyzed enantiomer-differentiating lactonization of y-hydroxy carboxylic acid esters with formation of butyrolactones substituted in... 

Devices that are able to regulate biochemical substances are of particular relevance for the implementation of systems substituting body functions, like that of the pancreas (Baldi et al. 2003). 

Interestingly, all of the candidate methods are ranked higher than injection, the system now routinely used. This is a good check by virtually any standard, insulin delivery by syringe and needle is a poor substitute for the pancreas. 

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