A cell simulator platform: the cell collective.

Diseases are often a result of multiple malfunctions in complex, nonlinear biological/biochemical networks. As such, these processes are far more complicated to understand because they tend to give rise to functions that are emergent in nature, i.e., higher-level (mal)functions that are more than the sum of their parts. Systems biology provides a new approach to understanding biological systems and diseases from a holistic perspective.

Efficacy of sustained release ciprofloxacin microspheres against device-associated Pseudomonas aeruginosa biofilm infection in a rabbit peritoneal model.

The relative effectiveness of a poly(L-lactic acid) ciprofloxacin hydrochloride (CIP) microsphere formulation (250-425 microns) against peritoneal implanted biofilm of Pseudomonas aeruginosa was investigated in a rabbit model. Correlations between in-vivo CIP pharmacokinetics in peritoneal dialysate and serum after intraperitoneal administration, in-vivo cell counts and rabbit survival rate were obtained. Dialysate and serum concentrations after 12 h (C12h) were greater than those obtained with free drug whereas maximum serum concentrations (Cmax) were lower and the time to reach Cmax(tmax) was longer. A silastic implant device pre-colonised with P. aeruginosa for 2 days was implanted in the rabbit peritoneum, and dialysate with or without drug or microspheres was administered via a catheter. Rabbits receiving no antibiotic and those receiving free drug (10 mg in dialysate) died of peritonitis and septicaemia, whereas all rabbits given CIP microspheres recovered completely from infection. The viable count of P. aeruginosa was markedly reduced or eliminated from the catheter, the device and the peritoneal wall in CIP microsphere-treated rabbits but not in rabbits treated with free drug, as determined from histological and scanning electronmicroscopic evidence. These results demonstrate that sustained release of antibiotics at biofilm eradication concentrations (BEC) is required to treat biofilm infections associated with peritoneal implanted devices.

Dose response of dairy cows to ammonium salts of volatile fatty acids.

In previous studies ammonium salts of a mixture of isobutyrate, 2-methylbutyrate, isovalerate, and valerate were fed in a corn silage, corn, corn gluten meal, and urea diet to Holstein cows throughout lactation to define the optimum level of ammonium salts of milk production. The objective of this work was to conduct another dose response study using other forage and protein sources and to determine the effects of decreasing VFA intakes as lactation advanced. The concentrate portion of the diet contained 0, .4, .8, 1.2, or 1.6% ammonium salts of VFA. The forage to concentrate ratio was 50:50, 60:40, and 70:30 for the first, middle, and last third of lactation, respectively. The study was conducted at four university locations using 191 Holstein cows. Feeds used included corn silage, alfalfa silage or hay, corn, soybean meal, minerals, and vitamins. Treatment x location interactions were significant for milk yield during early lactation. During mid- and late lactation, supplemental VFA (.8%) improved milk and protein yield. Milk composition was not greatly affected by feeding VFA. In mid-lactation, cows fed .8% ammonium salts of VFA ate more feed than did controls. Feed efficiencies were similar among groups throughout the experiment. Cows fed VFA tended to gain less BW during lactation than did controls. Health and reproduction were not different among groups.

The history, chemistry and pharmacokinetics of Sanguinaria extract.

Sanguinaria extract is a mixture of benzophenanthridine alkaloids derived from Sanguinaria canadensis L. (bloodroot). This mixture of alkaloids has a long history of use in tinctures and expectorants in pharmaceutical products. The purity of Sanguinaria extract is well defined. The chemistry and biochemistry of these alkaloids, including the dynamic equilibrium between acid and base forms, and pharmacokinetics of Sanguinaria extract shall be presented when this extract is incorporated into a dentifrice or oral rinse formulation.

Production responses of dairy cows fed various amounts of rumen-protected methionine and lysine.

A 3 x 3 factorial response surface design was used to study the effects of feeding rumen-protected methionine and lysine to dairy cows between 22 and 305 d of lactation. A total of 130 dairy cows at three universities were individually fed a corn silage and corn grain-based diet that contained either soybean meal or corn gluten meal and urea. An unsupplemented control diet plus nine treatment combinations of three amounts of rumen-protected DL-methionine (3.4, 7.8, and 12.2 g/d) and three amounts of rumen-protected L-lysine (5.9, 13.5, and 21.1 g/d) were fed at all locations. Plasma concentrations of methionine and lysine were increased when rumen-protected methionine and lysine were supplemented to the diets. Rumen-protected methionine and lysine did not affect feed intake by cows fed either by soybean meal or corn gluten meal and urea based diets. Milk protein percentage was increased, but milk and milk protein yields were not improved when diets containing soybean meal were supplemented with rumen-protected methionine and lysine. In contrast, milk and milk protein yields were improved when a diet that contained corn gluten meal and urea was supplemented with rumen-protected methionine and lysine. Health and reproduction measurements were similar for cows receiving all treatments.

Plasma amino acids and milk protein production by cows fed rumen-protected methionine and lysine.

Eighteen Holstein cows in midlactation were used to study the effectiveness of encapsulated rumen-protected methionine and rumen-protected lysine to deliver methionine and lysine postruminally. The experimental design was a 2 X 2 factorial, a center point, and a control treatment run in a partially balanced, incomplete block design. Treatments were administered over three periods of 3 wk. Cows were fed a blended diet consisting of corn silage, corn, and soybean meal supplemented with five different amounts of rumen-protected methionine and lysine. The amounts of DL-methionine and L-lysine (g/d), respectively, supplied from the encapsulated rumen-protected preparations for the six treatments were 1) 0, 0; 2) 10.40, 18.00; 3) 4.52, 7.82; 4) 16.28, 7.82; 5) 16.28, 28.18; and 6) 4.52, 28.18. In vitro results indicate that amino acids in both of the encapsulated preparations were 94% stable at a pH (5.4), which simulated the rumen, and 94% released at a pH (2.9), which simulated the abomasal environment. A linear increase of plasma methionine and lysine was observed as the amount of methionine and lysine supplied postruminally increased. The concentrations (microgram/ml) of methionine and lysine in plasma for the six treatments were 1) 2.47, 9.05; 2) 3.73, 11.59; 3) 3.60, 11.86; 4) 6.09, 10.45; 5) 5.28, 13.43; and 6) 3.33, 13.27. Rumen-protected lysine increased feed intake, milk yield, and 4% fat-corrected milk production within the surface treatments but had no effect when compared with the unsupplemented control treatment. Rumen-protected methionine and lysine increased production of milk protein. Lysine appeared to improve the utilization of methionine.

Microbial numbers, rumen fermentation, and nitrogen utilization of steers fed wet or dried brewers' grains.

Holstein steers were fed corn silage supplemented with either wet or dried brewers' grains to determine effects of heat drying commercial brewers' grains. Four rumen-fistulated steers were fed a 12.5% crude protein diet in a single reversal design experiment. Brewers' grains supplied 45% of the protein of the diet. Bacterial numbers, concentration of ciliated protozoa, and ammonia concentration in the rumen were higher, and rumen pH was lower, for steers fed wet brewers' grains. Concentrations of rumen volatile fatty acids were similar for both diets. Ruminal digestibility of dry matter decreased when wet versus dried brewers' grains were fed (56.9 versus 39.3%). The rate of dry matter passage from the rumen was faster with wet brewers' grains. In Experiment 2, 12 steers were in a 2 X 2 factorial design. Diets contained wet or dried brewers' grains supplemented at 22 or 40% of the diet dry matter (12.5 and 14.5% crude protein). Nitrogen retention was increased in steers fed the higher crude protein diet. Apparent digestible nitrogen, acid detergent fiber nitrogen, and nitrogen retention were higher with wet versus dried brewers' grains. Plasma essential and nonessential amino acids were also higher in steers fed wet brewers' grains. Alteration in microbial numbers, fermentation measurements, and nitrogen utilization were associated with more soluble nitrogen with wet (13.4%) versus dried (3.3%) brewers' grains.

Supplementation of dairy cow diets with ammonium salts of volatile fatty acids.

The objective was to determine the efficacy of a blend of ammonium salts of the volatile fatty acids, isobutyric, 2-methylbutyric, isovaleric, and valeric as a supplement to diets for dairy cows. Treatments of 0 (control) or 120 (supplemented) g/cow of the blend were fed daily from approximately 3 wk prepartum through a complete lactation. Five trials were conducted concurrently with a total of 116 multiparous Holstein cows. Dietary ingredients or combinations of ingredients differed in each of the trials. Diets contained either 1) corn gluten meal and urea, 2) soybean meal, or 3) cottonseed meal as the primary grain source of crude protein. The forage portion of the diets contained corn silage in combination with one or more of the following: alfalfa hay, alfalfa haylage, or wheat silage. Cows fed the supplement produced more milk and fat-corrected milk than the control cows for the 305-d lactation on four of the five diets, resulting in an average increase of 1.7 kg/d or 7%. Feed intake of cows on the supplemented diet was generally similar or lower than intake of the control cows throughout lactation, indicating that increased milk yield was associated with improved feed utilization. Percent milk fat was similar for cows on the supplemented diet, but fat yield was higher. Percent milk protein was lower for supplemented cows, but protein yield was about the same for both treatments because of higher milk yield. Health and reproduction were similar for all cows.

Milk production, nutrient digestion, and rate of digesta passage in dairy cows fed long or chopped alfalfa hay supplemented with sodium bicarbonate.

Effects of forage particle size and sodium bicarbonate on milk production, ruminal fermentation, ruminal fluid dilution rate, dry matter passage from the rumen, and nutrient digestion were measured in four Holstein cows in a 4 X 4 Latin-square experiment. Cows were fed ad libitum amounts of a diet of approximately 46% concentrate and 54% alfalfa hay. The 2 X 2 factorial arrangement of treatments were: 1) long stem alfalfa hay, 2) long stem alfalfa hay + 1.4% sodium bicarbonate (3.0% of concentrate), 3) chopped alfalfa hay (1.3 cm), and 4) chopped alfalfa hay + 1.4% sodium bicarbonate. Feed intake, milk yield, and milk composition were similar among treatments. Ruminal pH and concentration and molar percentages of volatile fatty acids were not altered. Decreasing feed particle size reduced ruminal fluid outflow as estimated by polyethylene glycol and chromium ethylenediamine tetraacetic acid dilution rates. Digestion of nutrients was decreased with chopped alfalfa hay but was not related to faster rate of passage of smaller size feed particles as determined by rare earth markers. Sodium bicarbonate increased water intake and tended to improve nutrient digestion. Absence of a significant effect of sodium bicarbonate upon rate of passage of chopped hay indicates that feed particles of this size are not significantly affected by small increases of dilution rate of ruminal fluid. Addition of sodium bicarbonate to an alfalfa hay (forage)-based diet did not improve production responses but did increase nutrient digestion.

Response of dairy cows to sodium bicarbonate and limestone in early lactation.

A total of 108 dairy cows at three locations were fed a diet supplemented with sodium bicarbonate and limestone during the first 16 wk of lactation. Complete mixed diets were fed for ad libitum intake and consisted of concentrate and corn silage (60:40, dry matter). The four treatments were: 1) basal diet, 2) basal plus 1.2% sodium bicarbonate, 3) basal plus 1.4% limestone, and 4) basal plus 1.2% sodium bicarbonate plus 1.4% limestone. Dry matter intake was increased for 8 wk by sodium bicarbonate, then decreased from wk 9 to 16. Intake was decreased by limestone alone or in combination with sodium bicarbonate. Sodium bicarbonate increased milk production for 8 wk and 4% fat-corrected milk for 16 wk. Average dry matter intake, milk production, and 4% fat-corrected milk (kg/day) for the 16 wk were: 1) 20.2, 31.1, 27.3; 2) 19.8, 32.0, 28.7; 3) 18.9, 31.4, 27.9, and 4) 18.4, 29.7, 27.2 for diets 1 to 4. Ruminal pH was decreased, and volatile fatty acid concentration was increased by added sodium bicarbonate and appeared to result from increased feed intake. Digestibility of nutrients was unaffected by supplements. Sodium bicarbonate affected regulation of blood and urine pH and concentration of electrolytes more than limestone. Serum magnesium was reduced with sodium bicarbonate, although not beyond normal physiological reference range.