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Biomedical subjects

D J Pollard

Publications and source records attributed to D J Pollard.

8 recordsLinked to original sources
PubMed2007

Scale up of a viscous fungal fermentation: application of scale-up criteria with regime analysis and operating boundary conditions.

The scale up of the novel, pharmaceutically important pneumocandin (B(0)), from the filamentous fungus Glarea lozoyensis was successfully completed from pilot scale (0.07, 0.8, and 19 m(3)) to production scale (57 m(3)). This was accomplished, despite dissimilar reactor geometry, employing a combination of scale-up criteria, process sensitivity studies, and regime analysis using characteristic time constants for both oxygen mass transfer and bulk mixing. Dissolved oxygen tension, separated from the influence of agitation by gas blending at the 0.07 m(3)-scale, had a marked influence on the concentrations of pneumocandin analogs with different levels of hydroxylation, and these concentrations were used as an indicator of bulk mixing upon scale up. The profound impact of dissolved oxygen tension (DOT) (low and high levels) on analog formation dictated the use of constant DOT, at 80% air saturation, as a scale-up criterion. As a result k(L)a, Oxygen uptake rate (OUR) and hence the OTR were held constant, which were effectively conserved across the scales, while the use of other criterion such as P(g)/V(L), or mixing time were less effective. Production scale (57 m(3)) mixing times were found to be faster than those at 19 m(3) due to a difference in liquid height/tank diameter ratio (H(L)/D(T)). Regime analysis at 19 and 57 m(3) for bulk mixing (t(c)) and oxygen transfer (1/k(L)a) showed that oxygen transfer was the rate-limiting step for this highly shear thinning fermentation, providing additional support for the choice of scale-up criterion.

Ascomycota↗
PubMed2006

Asymmetric reduction of alpha, beta-unsaturated ketone to (R) allylic alcohol by Candida chilensis.

A pilot scale whole cell process was developed for the enantioselective 1,2-reduction of prochiral alpha,beta-unsaturated ketone to (R) allylic alcohol using Candida chilensis. Initial development showed high enantiomeric excess (EE > 95%) but low product yield (10%). Process development, using a combination of statistically designed screening and optimization experiments, improved the desired alcohol yield to 90%. The fermentation growth stage, particularly medium composition and growth pH, had a significant impact on the bioconversion while process characterization identified diverse challenges including the presence of multiple enzymes, substrate/product toxicity, and biphasic cellular morphology. Manipulating the fermentation media allowed control of the whole cell morphology to a predominantly unicellular broth, away from the viscous pseudohyphae, which were detrimental to the bioconversion. The activity of a competing enzyme, which produced the undesired saturated ketone and (R) saturated alcohol, was minimized to < or =5% by controlling the reaction pH, temperature, substrate concentration, and biomass level. Despite the toxicity effects limiting the volumetric productivity, a reproducible and scaleable process was demonstrated at pilot scale with high enantioselectivity (EE > 95%) and overall yield greater than 80%. This was the preferred route compared to a partially purified process using ultra centrifugation, which led to improved volumetric productivity but reduced yield (g/day). The whole cell approach proved to be a valuable alternative to chemical reduction routes, as an intermediate step for the asymmetric synthesis of an integrin receptor antagonist for the inhibition of bone resorption and treatment of osteoporosis.

Biotransformation↗
PubMed2002

Pilot-scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins.

The filamentous fungus Glarea lozoyensis produces a novel, pharmaceutically important pneumocandin (B(0)) that is used to synthesize a lipopeptide which demonstrates cidal activity against clinically relevant pathogens. A range of unwanted pneumocandin analogs are also produced by the organism. To maintain the unwanted impurities to acceptable levels upon scaleup, a good understanding of the impact of chemical and physical environment on the cell physiology is required, which benefits downstream processing. Pilot-scale studies were performed to determine the impact of dissolved oxygen, temperature, pH, and carbon dioxide on the process. Experiments included multiple fermenters (up to seven) at 0.07 and 0.8 m(3) scale using single source medium sterilization and inoculum. Gas blending was used to separate effects of dissolved oxygen from agitation. The process was significantly influenced by dissolved oxygen level. The critical dissolved oxygen tension (C(crit)) for growth was below 2% air saturation. The C(crit) for production of pneumocandin B(0) was 20% air saturation, with a significant reduction of the specific production rate below this value. In contrast, low dissolved oxygen levels produced a substantial increase of pneumocandins B(1), B(5), and E(0), while high dissolved oxygen levels produced a disproportionate increase of D(5). This sensivity to dissolved oxygen was independent of agitation within a power range of 2-15 kW/m(3). Broth viscosity was impacted below 10% dissolved oxygen, suggesting an effect on morphology. The process was shown to be sensitive to temperature but relatively insensitive to pH and carbon dioxide (in the exhaust gas) within the ranges studied. This scaledown analysis explained phenomena seen at pilot scale and helped define operating boundary conditions for successful scale up to 19 m(3).

Anti-Bacterial Agents↗
PubMed1998

Development and evaluation of a computer-aided learning package for minor oral surgery teaching.

'Aspects of Minor Oral Surgery' is a highly interactive software program that was commissioned by the Department of Health, England, as part of the continuing education opportunities of general dental practitioners. The content of the program is also suited to the education of senior clinical dental students. The beta (pre-release) version was evaluated by 67 general dental practitioners, who completed a questionnaire on aspects of the program's functionality. Responses on its usefulness as an educational tool were 78% positive and 4% negative. In comparing the program to other educational media on the same subject, 77% felt it was better than video, 69% said it was better than textbooks, and 80% preferred it to journals. Its main strengths were judged to be the high level of interactivity, the ease of navigation and use, and the quiz section. The quality of the images of surgical procedures displayed in the slide shows was judged to be a weakness, and this problem was addressed in preparing the final version. Ten UK academic and four health service senior oral surgeons were also asked to give feedback on the program's content, and these points were also incorporated in the final text. More than 1,600 copies of the program have been taken up by general dental practitioners so far. The program may be downloaded for evaluation via the internet.

Adult↗
PubMed1997

Should clinical lecturers produce their own CAL material?

Clinical lecturers may embark upon the task of creating CAL material unaware of the effort required to produce the simplest of programs. This study aimed to measure the effort involved in such a task in order that those contemplating such development might make a judgement which is well informed. The study entailed a computer literate, yet non-programming clinical lecturer producing a ten-minute CAL program using three different authoring templates. A diary and time log were kept. The resulting pleces of software are discussed as well as the process by which they were created.

Computer-Assisted Instruction↗
PubMed1987

Survival of Listeria monocytogenes in milk during high-temperature, short-time pasteurization.

Milk from cows inoculated with Listeria monocytogenes was pooled for 2 to 4 days and then heated at 71.7 to 73.9 degrees C for 16.4 s or at 76.4 to 77.8 degrees C for 15.4 s in a high-temperature, short-time plate heat exchanger pasteurization unit. L. monocytogenes was isolated from milk after heat treatment in six of nine pasteurization trials done at 71.7 to 73.9 degrees C and in none of three trials done at 76.4 to 77.8 degrees C. An average of 1.5 to 9.2 L. monocytogenes cells was seen in each milk polymorphonuclear leukocyte before heat treatment in 11 of 12 pasteurization trials. Noticeable degradation of leukocytes with intracellular listeria was detected in unpasteurized milk after 3 days of storage at 4 degrees C, and by 4 days of storage leukocytes had deteriorated to cellular debris, suggesting that holding unpasteurized milk refrigerated for 4 or more days would eliminate a protective effect leukocytes may provide for increasing heat resistance of L. monocytogenes. Results indicate that under the conditions of this study, L. monocytogenes can survive the minimum high-temperature, short-time treatment (71.7 degrees C, 15 s) required by the U.S. Food and Drug Administration for pasteurizing milk.

Animals↗
PubMedDate not supplied

An evaluation of training general dental practitioners in partial denture design using a computer-assisted learning program.

The authors of this paper produced a computer-assisted learning (CAL) program on aspects of partial denture design which covered the topics of surveying, support and indirect retention. Version 1 of the program was evaluated by 65 general dental practitioners, the majority of whom did this at their own homes or practices whilst the rest came in to the School of Dentistry. Participants were of varied ages and computer experience. A total of 85% of the participants found the program easy to use and 78% claimed the program had improved their knowledge of partial denture design, although less than half thought it had improved their practical skills. Opinions varied on which of the three topics were the most useful, and interest in future CAL material for dentistry was high. The study shows that CAL can be an acceptable, effective and enjoyable form of training for general dental practitioners who have access to modern microcomputers.

Adult↗