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[Principles for optimizing and guaging several processes in the technology of vaccine production. I. Several problems in guaging and optimizing thermal sterilization of fluids].

Thermal sterilization of fluids--one of the widespread operations in microbiological laboratories and in vaccine production--solves two tasks: provides sterility and maximal preservation of biological value of the sterilized fluid. A possibility and expediency of using some indices for the quantitative assessment of the efficacy of the sterilization regimens, including measurement of the sterilization processes is considered in this work. A possible way of the regimen optimization on the basis of known values of the activation energies of the processes of decomposition of thermolabile components and inactivation of foreign microbial flora is assessed.

Hot Temperature

Optimization of a process for the production of (R)-2-hydroxy-4-phenylbutyric acid--an intermediate for inhibitors of angiotensin converting enzyme.

(R)-2-Hydroxy-4-phenylbutyric acid, an intermediate in the manufacture of inhibitors of angiotensin converting enzyme, can be produced continuously in an enzyme membrane reactor by enzymatic reduction of its corresponding alpha-keto acid. D-Lactate dehydrogenase (D-LDH) from Staphylococcus epidermidis was chosen as the most appropriate enzyme to carry out the NADH-dependent reduction. Formate dehydrogenase (FDH) was used for NADH regeneration. Detailed kinetic measurements and a mathematical model for the coupled enzyme reactions were applied to calculate the optimal conditions for continuous production of the alpha-hydroxy acid. A mass of 1 kg [corrected] (R)-2-hydroxy-4-phenylbutyric acid was synthesized in a 220 ml enzyme membrane reactor over a period of 4 weeks. A mean space-time-yield of 165 g l-1 d-1 was achieved at low enzyme consumptions of 150 U kg-1 alpha-hydroxy acid for FDH and D-LDH.

Angiotensin-Converting Enzyme Inhibitors

Optimizing the biolistic process for different biological applications.

The biolistic process is still rapidly evolving. We do not anticipate further major improvements in biolistic apparatus. There will probably still be further major improvements in particles, DNA coating, and vectors, as well as significant further advances in understanding of biological determinants of cell penetration and survival. The technology has currently reached the point at which it can be readily and reliably used for a wide range of applications. Given the information presented in this chapter, new applications can be optimized fairly readily.

Animals

Cytologic evaluation of serous effusions. Processing techniques and optimal number of smears for routine preparation.

A double-blind retrospective review of 90 pleural and ascitic fluids was performed to determine the optimal number of smears necessary to produce an accurate evaluation, and to analyze the utility of different preparation techniques. Each case had four Papanicolaou-stained smears (two alcohol fixed and two Saccomanno fixed) and one Diff-Quik-stained, air-dried smear. Forty cases originally were reported as positive (37 adenocarcinoma, 1 lymphoma, and 2 Pneumocystis carinii) and 50 were reported as negative. The results showed that the diagnostic yield of evaluating five smears compared with three (one of each preparation) is identical. Air-dried smears were the most sensitive in identifying malignant cells and infectious organisms. It is concluded that (1) the diagnostic accuracy is enhanced by the use of several preparation techniques to include air-dried smears and (2) when variable processing methods are used, the evaluation of more than three smears does not increase the diagnostic yield.

Adenocarcinoma

Model aided dynamic process analysis and optimization for the nourseothricin fermentation.

The relation between product formation and growth kinetics could be characterized by two facts: the specific product formation rate depends on the ageing of the population and on the specific growth rate. These relation was formulated and quantified by a mathematical model, which was fitted to experimental data of a representative fermentation run und used to predict an optimal fermentation mode. In the result of this discussion cyclic fed batch fermentation was found to be optimal.

Anti-Bacterial Agents

The role of glucocorticoid hormones as biological amplifiers.

Recent research in hormone action has been aimed at studying single effects in well-defined systems. As exemplified in several chapters of this book, it has been possible to deduce a general mechanism of action of the glucocorticoids using this approach. Most hormones, and the glucocorticoids in particular, do not act as independent agents in the intact animal. Although the best known example of how glucocorticoids interact with other hormones is the amplification of the effect of those whose action is mediated by cAMP, these steroids also augment the effects of a variety of other hormones and effectors. Such interactions are of interest in clinical medicine as well, since glucocorticoid hormones are used in combination with other drugs in a number of conditions, including the treatment of asthma, allergies, and certain kinds of shock and cancer. Neither the biochemical nor the pharmacologic basis for the effects of the glucocorticoids is known. In some cases the actions of other hormones are not observed unless the tissue has first been exposed to glucocorticoids. In these instances the glucocorticoids are said to exert a "permissive effect," since they allow a process to proceed at a maximal rate even though the steroid itself has no effect on this process. There is no doubt that such examples exist, as documented above: thus the concept of a "permissive effect" does have utility. The term fails to describe the more general role the glucocorticoids play, since in many instances the steroid also has a direct effect on the process itself, or optimizes a process in which the primary effector is not as yet known. Because of these cases, and because the historically more general usage first proposed by INGLE [1] seems to have been forgotten, use of the term "permissive effect" has been avoided in this chapter. An ultimate goal in glucocorticoid hormone research is to identify the mechanisms involved in the amplification effect these hormones exert. Now that the actions of these hormones and of the hormones they interact with are being defined, such work is within the realm of feasibility.

Animals

Optimizing performance through process improvement.

Health care professionals have found traditional problem solving and traditional management have not succeeded in "assuring quality." Organizations are changing the way they do business and are utilizing process improvement methodology to improve performance. Based on important functions, select dimensions of performance for processes are measured, evaluated, redesigned, and improved. Once priorities for improvement activities are determined, improvement projects can be implemented utilizing various process improvement models. The PRIDE (process, relevant, interpret, design, execute) model, designed by the authors, is one approach that can be applied in any setting.

Efficiency, Organizational

Standardization of process parameters for salbutamol sulphate microcapsules coated with cellulose acetate phthalate and computation of in-vitro release kinetics.

Salbutamol sulphate, a bronchodilatatory drug for asthma, is encapsulated by Emulsion-Solvent-Evaporation technique using cellulose acetatephthalate as coating polymeric material. Different process parameters like Stirring Speed, Drug-Polymer Ratio, Solvent-Polymer Ratio, Internal Phase-External Phase Ratio, Effects of Temperature, and of Surfactants have been studied to standardise the process. At optimal condition of process parameters maximum encapsulation efficiency is obtained and microcapsules produced are free flowing and spherical. The dissolution of the microcapsules is carried out and the data obtained from in-vitro dissolution profile are computed in the light of different kinetic models. Diffusion coefficient (Da) and diffusivity rate constant (KBL) are evaluated with the help of Baker-Lonsdale model.

Albuterol

[Ways to optimize the technological process of oleandomycin reextraction].

Dependence of the oleandomycin distribution coefficient on pH of the acqueous phase and temperature in the system of butylacetate extract-water acidified with orthophosphoric acid was studied. With a purpose of intensification of the process of oleandomycin reextraction, decreasing the antibiotic inactivation and evaporation of the organic solvent it was proposed to perfom oleandomycin extraction at pH 4.0--5.0 accompanied by simultaneous decreasing of the temperature.

Acetates

[Optimizing the learning process in short-term autogenic training by practice protocols].

The results of two studies are presented, in which the question was investigated, whether the learning process of autogenic training (AT) in short group programs can be improved by the use of a self-control technique (records for the AT-exercises realized without the group at home). Study I refers to 24 university students, who learned AT within their psychology education; Study II refers to 28 adults, who learned AT within a psychosocial community service for adults. Within control-group designs evaluative and follow-up data were gathered before, during, at the end, and 4 months after the AT-treatment. The data refer to psychosomatic complaints (SSP, ATSYM), depression (BDI), relaxation capacity and wellbeing (VFE) as well as subjective valuations of AT and the frequency of AT-exercising. The results of both studies show that the basal AT-exercises can be learned in short group programs (6 meetings within 6 weeks). The self-control technique promotes the learning process at short as well as at longer sight. Implications of the results for the realization of introductions to AT in out- and in-patient group treatment are discussed.

Adult