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glands by means of a gene therapy vector, and (c) the generation of infection-resistant transgenic animals expressing the lysostaphin gene in their mammary glands The rst approach relies on the intramammary administration of recombinant lysostaphin to infected animals In one such study, 30 dairy cattle were infected with S aureus and subsequently administered, through the teat canal, recombinant lysostaphin dissolved in phosphate-buffered saline (PBS), sodium cephapirin in PBS, or a commercial preparation of cephapirin (Oldham and Daley 1991) It was found that the minimum effective therapeutic dose of lysostaphin was 100 mg Administration of one 100-mg dose of the enzyme resulted in maintaining the lysostaphin MBC in milk for up to 36 48 h.

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That lysostaphin is fairly stable in milk was also shown in another experiment in which incubation of the enzyme in milk at 37 C for 72 h did not lead to a signi cant decrease in lysostaphin s antibacterial activity The cure rate in animals that received lysostaphin at the dose of 100 mg was 20% compared with 29% and 57% for sodium cephapirin in PBS and its commercial preparation, respectively In fact, although after the administration of lysostaphin no staphylococci were detected in the majority of the animals, the overall ef cacy of the treatment was decreased by relatively quick relapses, likely caused by bacteria internalized by cells of the mammary glands.

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where F(t) is the fraction of material leaving the pipe before a given time t Notice that no uid leaves a pipe before one-half the residence time and that at the average residence time half the material has left F(t) can also be though of as the well-mixed normalized concentration exiting the pipe In actuality the ow leaving a pipe is radially distributed, but F(t) as a normalized concentration is the concentration it would be if there was instantaneous mixing at the end of the pipe This distribution can cause many problems in treatment and reactions in laminar ow In most cases, plug ow where all parts of the uid spend the same time in the pipe is preferred Static mixing technology is very applicable to slow chemical reactions requiring plug ow for long duration (see Streiff and Rogers, 1994).

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Furthermore, in view of the large difference in therapeutic ef cacy between cephapirin in PBS and its commercial preparation (containing the antibiotic formulated in a peanut oil base), the authors suggested that lysostaphin could also be much more ef cacious in an improved formulation The second approach to preventing or treating mastitis relies on the introduction of the lysostaphin gene to the mammary gland cells of individual animals The effectiveness of this approach was evaluated by Fan et al, who employed a replication-de cient human adenoviral vector containing a modi ed lysostaphin gene In the rst experiment, the adenoviral vector was used to transduce bovine mammary gland epithelial cells in vitro, which resulted in the production and release of functional lysostaphin into cell culture medium While the lysostaphin concentration in the culture medium reached 0.

8 g/ml, its biological activity was at a level of 20% of that typical of recombinant lysostaphin produced by bacteria In the second major experiment, the same vector, administered by intramammary infusion, was used to transduce mammary gland cells of nonlactating goats in vivo Lysostaphin expression in the mammary glands did not appear to adversely affect the health of the animals The enzyme s concentration in the secretions of the mammary glands ranged from 02 to 06 g/ml on day 1 after infusion and from 09 to 11 g/ml on day 2 postinfusion These.

Plug ow is achievable with SMX and SMXL static mixers, and with the SMR when precise control of temperature during reaction is also important Mixing and heat transfer criteria have already been discussed Reaction presents additional requirements and constraints on the design First laboratory, and then pilot testing is almost always necessary to establish full scale reactor design The static mixer reactor is preferably a monotube design Multitube con guration presents high potential for reactor instability and nonperformance due to tube tube variation, as described previously This is especially true when attempting to control high viscosity exothermic polymerization reactions (Nguyen et al, 1984b; Cusack, 1999) Commercial scale tubular plug ow reactors utilizing SMX and SMXL static mixer internals have now been operating for more than 20 years These static mixer designs have demonstrated their ability to mix and achieve plug ow in large scale equipment.

pp.112-121. IEEE Computer Society Press,

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