Fibre degradation of wheat straw by Pleurotus erygnii under low moisture conditions during solid-state fermentation.

The application of solid-state fermentation offers an alternative to conventional, submerged approaches for a variety of bioconversion processes, including animal feeds, biofuels and fungal bioproducts. Optimizing solid-state fermentation under low moisture conditions could significantly impact the proportion of dry biomass that could be processed and improve the commercial viability of this approach, because of reduced input costs and higher yields of final products. Pleurotus erygnii that appeared to show tolerance to low moisture conditions was grown on saturated and desaturated wheat straw. Pleurotus erygnii showed insignificant fibre degradation although showed significantly lower biomass decomposition on desaturated wheat straw. Fibre decomposition by the fungus on wheat straw containing wheat bran showed marginally higher decomposition when saturated although there was no difference in biomass decomposition. The levels of delignification achieved were similar under different saturation conditions. It would appear that the fungus effectively decomposed fibre under low moisture conditions often resulting in lower biomass losses. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, a white rot fungus, Pleurotus erygnii, effectively decomposed fibre under low moisture conditions when grown on wheat straw at similar levels under higher moisture conditions. However, the addition of wheat bran to wheat straw created a heterogeneous system that appeared to allow P. erygnii to thrive under much lower moisture conditions although lower levels of fibre decomposition was obtained. These factors could influence the preparation of solid-state fermentation.

A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation.

BACKGROUND: Adding a fixed dose of 1 g b.i.d. of mycophenolate mofetil (MMF) to an immunosuppressive regimen consisting of cyclosporine and prednisone results in a 50% reduction in the incidence of acute rejection after kidney transplantation. This study was designed to investigate the relationship between pharmacokinetic data (mycophenolic acid area under the curve; MPA AUC) and the prevention of rejection after kidney transplantation. METHODS: A total of 154 adult recipients of a primary or secondary cadaveric kidney graft were randomly allocated, in this double-blind trial, to receive MMF treatment aimed at three predefined target MPA AUC values (16.1, 32.2, and 60.6 microg x hr/ml). During the first 6 months after transplantation, plasma samples for nine AUCs were collected. After analysis of the samples, a coded dose adjustment advice was generated using a Bayesian algorithm, maintaining the double blinding. Immunosuppressive therapy further consisted of cyclosporine and prednisone. The primary end point of this study was the occurrence of biopsy-proven acute rejection within the 6-month study period. RESULTS: A total of 150 patients were eligible for analysis. Although after day 21, the mean MMF dose was reduced, the mean MPA AUC gradually increased and target MPA AUC values were exceeded in all three groups. The incidences of biopsy-proven acute rejection in the low, intermediate, and high target MPA AUC groups were 14 of 51 (27.5%), 7 of 47 (14.9%), and 6 of 52 (11.5%), respectively. The incidences of premature withdrawal from the study due to adverse events in the three groups were 4 of 51 (7.8%), 11 of 47 (23.4%), and 23 of 52 (44.2%), respectively. Logistic regression analysis showed a highly statistically significant relationship between median ln(MPA AUC) and the occurrence of a biopsy-proven rejection (P<0.001). The logistic regression using median ln(Cpredose) was also statistically significant for this relationship (P=0.01), whereas it was not when using mean MMF dose (P=0.082). In contrast, the logistic regression using mean MMF dose for comparison of patients who successfully completed the study versus patients experiencing premature withdrawal due to adverse events was highly significant (P<0.001), whereas this was not significant when using median ln(Cpredose) (P=0.512) or median ln(MPA AUC) (P=0.434). CONCLUSION: MPA Cpredose and MPA AUC are significantly related to the incidence of biopsy-proven rejection after kidney transplantation, whereas MMF dose is significantly related to the occurrence of adverse events.

The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation.

BACKGROUND: Mycophenolate mofetil, a pro-drug for mycophenolic acid, reduces the likelihood of allograft rejection after renal transplantation. We studied the relationship between mycophenolic acid pharmacokinetics and the likelihood of rejection in a randomized concentration-controlled trial. METHODS: Under double-blind conditions, recipients of kidney transplants were followed for evidence of allograft rejection for 6 months. In addition to mycophenolate mofetil, patients received usual doses of cyclosporine (INN, ciclosporin) and corticosteroids. The dose of mycophenolate mofetil (given twice daily) was controlled by feedback, with mycophenolic acid area under the concentration-time curve (AUC) as the controlled variable. Patients were randomly assigned to 1 of 3 target AUC groups. RESULTS: Logistic regression analysis showed a significant (P < .0001) relationship between mycophenolic acid AUC and the likelihood of rejection. High mycophenolic acid values were associated with a very low probability of rejection. An AUC of 15 micrograms.h/mL yielded 50% of maximal achievable efficacy with a 4% change of efficacy for a 1 microgram.h/mL change in AUC at the midpoint of the logistic curve. Exploratory analyses showed other variables (e.g., the maximum observed plasma concentration, predose plasma concentration, and drug dose) had poorer predictive power for the rejection outcome. Bivariate regression confirmed the importance of AUC as a highly predictive variable and showed low predictive value of other variables, once the contribution of AUC had been considered. The characteristic side effects of mycophenolate mofetil therapy appeared related to drug dose but not to mycophenolic acid concentration. CONCLUSIONS: The AUC of mycophenolic acid is predictive of the likelihood of allograft rejection after renal transplantation in patients receiving mycophenolate mofetil.

Fate in sewage of a recombinant Escherichia coli K-12 strain used in the commercial production of bovine somatotropin.

The fate of a derivative of Escherichia coli strain W3110G [pBGH1], a strain used for production of bovine somatotropin, was examined in semi-continuous activated sludge (SCAS) units. A nalidixic acid-resistant derivative of W3110G [pBGH1], strain LBB270 [pBGH1], was used to facilitate tracking. SCAS units (300 ml) containing municipal mixed liquor were operated on a daily cycle of 23 h aeration and 1 h setting followed by decanting of clear supernatant (175 ml) and refilling with fresh primary effluent. SCAS units were inoculated with two concentrations of E. coli LBB270 [pBGH1] and operated for 200 h. Viable levels of E. coli LBB270 [pBGH1] were measured daily in aerated mixed liquor and decanted supernatant. Viable counts in the mixed liquor decreased from 10,000- to 100,000-fold in less than 200 h. Losses of E. coli LBB270 [pBGH1] in decanted supernatants accounted for less than 2-fold of the total losses observed in the SCAS units. The E. coli LBB270 [pBGH1] was not evenly distributed in the mixed liquor, but became preferentially associated with the settleable floc. These results show that E. coli LBB270 [pBGH1] was unable to survive in municipal sludge even when inoculated at concentrations greater than, or comparable to, levels of indigenous microorganisms.

Long-term effects of sometribove in lactating cows during a fourth consecutive lactation of treatment: insulin and somatotropin responses to glucose infusion.

The effect of sometribove (USAN, methionyl bST) on the endocrine pancreas and blood bST concentrations was investigated in 6 control and 6 treated Friesian cows, averaging 111 and 118 d postpartum in their fourth lactation of treatment. Each lactation the treated cows received sometribove injections (500 mg) every 2 wk (injection cycle) starting 60 +/- 3 d postpartum, increasing milk yield 3.3, 5.9, 1.9, and 4.2 kg/d in lactations 1, 2, 3, and 4, respectively. On d 8 of a fourth lactation injection cycle, blood was sampled for 390 min, starting 30 min before an intravenous glucose infusion (100 mg/kg) over a 20-min period. Preinfusion concentrations of glucose, insulin, and bST were elevated in sometribove-treated cows versus controls: 82.1 versus 74.4 mg/dl, 28.1 versus 19.7 microIU/ml, and 4.6 versus .9 ng/ml, respectively. Glucose infusion resulted in a rapid increase in blood glucose and insulin concentrations, followed by a sharp decline to preinfusion values across both treatments, resulting in similar net area under the curves for glucose and insulin. Blood bST concentrations remained unchanged. This study supports the concept that sometribove increases milk yield in dairy cows by chronically influencing homeorhetic mechanisms.

Fate in water of a recombinant Escherichia coli K-12 strain used in the commercial production of bovine somatotropin.

The fate in water of Escherichia coli K-12 strain LBB269, both plasmid-free and carrying the recombinant plasmid pBGH1, was studied. E. coli K-12 strain LBB269 (pBGH1) is a nalidixic acid resistant derivative of W3110G (pBGH1), the microorganism used by Monsanto Company for the commercial production of bovine somatotropin. Water samples were obtained from the Missouri River and from the Monsanto Life Sciences Research Center aqueous waste basin. Strains LBB269 and LBB269 (pBGH1) were grown in fermentation vessel under bovine somatotropin (BST) production conditions, and inoculated into the water samples. The inoculated water samples were incubated at 26 degrees C, and the number of viable E. coli cells was determined as a function of time. In sterile water from both sources, the two strains remained at a constant level for at least 28 days; LBB269 (pBGH1) remained at a constant level in sterile water for at least 300 days. In non-sterile water from both sources, the two strains declined from an initial concentration of about 3.0 x 10(6) cells per ml to less than 10 cells per ml in 147 h. The study conditions did not adversely affect the populations of indigenous microorganisms. The selective loss of strains LBB269 and LBB269 (pBGH1) demonstrates that these E. coli strains do not survive in environmental sources of water. In addition, it was observed that the presence of pBGH1 had essentially no effect on the disappearance of strain LBB269 from either source of water.

Precision of the all-glass impinger and the andersen microbial impactor for air sampling in solid-waste handling facilities.

A method was devised to determine the precision of the all-glass impinger and the Andersen six-stage microbial impactor over a wide range of aerosol concentrations like those found in facilities which process solid waste. Simultaneous samples were collected inside a municipal solid-waste recovery system, and the data were treated statistically to estimate the precision of each air-sampling device. All-glass impingers yielded colony counts which indicated a linear relationship between samplers over an observed aerosol concentration of 1.1 X 10(3) to 2.8 X 10(7) colony-forming units per m3 of air. Impactors also yielded colony counts which indicated a linear relationship over an observed aerosol concentration range of 3.9 X 10(3) to 1.9 X 10(5) colony-forming units per m3 of air. The coefficients of variation for the all-glass impinger and the six-stage impactor in an environment with a high and variable dust level were determined to be 0.38 and 0.23, respectively.