Porous and strong three-dimensional carbon nanotube coated ceramic scaffolds for tissue engineering.

Biomaterials research is investigating increasingly complex materials capable of mirroring the highly organized biochemical and architectural environments of the body. Accordingly, tissue scaffolds with nanoscale properties that mirror the fibrous proteins present in tissue are being developed. Such materials can benefit from the inherent dimensional similarities and nanocomposite nature of the cellular environment, altering nanoscale dimensional and biochemical properties to mimic the regulatory characteristics of natural cellular environments. One nanomaterial which demonstrates potential across a diverse range of biomaterial applications is carbon nanotubes (CNTs). Building on previous reports, a method to coat CNTs throughout 3D porous structures is developed. Through modifications to typical chemical vapour deposition (CVD), a high-quality uniform coating of carbon nanotubes (CNTs) is demonstrated over ß-tricalcium phosphate/hydroxyapatite (or TCP/HA), which is in clinical use; and the high-mechanical-strength multicomponent ceramic Ca2ZnSi2O7-ZnAl2O4, (or Sr-HT-Gah). The resulting materials address deficiencies of previously reported CNT biomaterials by simultaneously presenting properties of high porosity, biocompatibility and a mechanical stability. Together, this unique combination of properties makes these scaffolds versatile materials for tissue engineering in load bearing applications.

Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells.

Numerous studies have suggested an important role for the Th2 cytokines interleukin (IL)-13 and IL-4 in the development of allergic asthma. We tested the hypothesis that IL-13 and IL-4 have direct effects on cultured airway smooth muscle cells (HASM). Using RT-PCR, we showed that HASM cells express transcripts for IL-4alpha, IL-13RalphaI, and IL-13RalphaII, but not for the common IL-2Rgamma chain. We then analyzed the capacity of the two cytokines to activate signaling pathways in HASM cells. Both IL-13 and IL-4 caused STAT-6 phosphorylation, but the time course was different between the two cytokines, with peak effects occurring 15 min after addition of IL-4 and 1 h after addition of IL-13. Effects on signaling were observed at cytokine concentrations as low as 0.3 ng/ml. IL-4 and IL-13 also caused phosphorylation of ERK MAP kinase. As suggested by the signaling studies, the biological responses of the two cytokines were also different. We used magnetic twisting cytometry to measure cell stiffness of HASM cells and tested the capacity of IL-4 and IL-13 to interfere with the reductions in cell stiffness induced by the beta-agonist isoproterenol (ISO). IL-13 (50 ng/ml for 24 h), but not IL-4, significantly reduced beta-adrenergic responsiveness of HASM cells, and the MEK inhibitor U0126 significantly reduced the effects of IL-13 on ISO-induced changes in cell stiffness. We propose that these direct effect of IL-13 on HASM cells may contribute at least in part to the airway narrowing observed in patients with asthma.

Short-chain fatty acid metabolism, apoptosis, and Apc-initiated tumorigenesis in the mouse gastrointestinal mucosa.

Short-chain fatty acids (SCFAs) are physiological regulators of growth and differentiation in the gastrointestinal tract, and we have previously shown that apoptosis induced in colonic cell lines by these compounds is dependent on their metabolism by B-oxidation in the mitochondria (B. G. Heerdt et al., J. Biol. Chem., 266: 19120-19126, 1991; Cancer Res., 54: 3288-3293, 1994). Because tumors initiated by an inherited Apc mutation have been reported to be linked to decreases in apoptosis in the flat mucosa of the gastrointestinal tract, the aims were to determine whether elimination of efficient metabolism of SCFAs affected apoptosis in the gastrointestinal mucosa of the mouse, and whether this altered tumorigenesis initiated by an inherited Apc mutation. We, therefore, generated mice that have a chain-terminating mutation in the Apc gene and that were either wild-type for SCFA metabolism, or deficient, due to homozygous deletion of the gene (Scad) that encodes the enzyme short-chain acyl dehydrogenase, which catalyzes the first step in SCFA B-oxidation. Scad+/+ mice maintained on a wheat bran-fiber-supplemented diet gained significantly more weight than mice maintained on AIN76A, but this was eliminated by the Scad mutation, demonstrating that uptake and metabolism of SCFAs in the gastrointestinal tract can be a significant energy source. As predicted, on either AIN76A or wheat bran diet, the Scad mutation almost completely eliminated apoptosis in the flat mucosa of the proximal colon and reduced apoptosis by 50% in the distal colon compared with littermates that were wild-type for Scad. The mutation also reduced apoptosis by approximately 50% in the duodenum in AIN76A-fed mice. These reductions in apoptosis had no effect on incidence, frequency, or site specificity of tumors initiated by the Apc mutation. Therefore, the metabolism of SCFAs by the gastrointestinal mucosa plays a role in modulating apoptosis, but a general decrease in apoptosis in the mucosa of the gastrointestinal tract is not linked to gastrointestinal tumorigenesis initiated by an inherited Apc mutation.

Observations on animal and human health during the outbreak of Mycobacterium bovis in game farm wapiti in Alberta.

This report describes and discusses the history, clinical, pathologic, epidemiologic, and human health aspects of an outbreak of Mycobacterium bovis infection in domestic wapiti in Alberta between 1990 and 1993, shortly after legislative changes allowing game farming. The extent and seriousness of the outbreak of M. bovis in wapiti in Alberta was not fully known at its onset. The clinical findings in the first recognized infected wapiti are presented and the postmortem records for the herd in which the animal resided are summarized. Epidemiologic findings from the subsequent field investigation are reviewed, the results of recognition and investigation of human exposure are updated, and recommendations for reduction of human exposure are presented.

The influence of feedlot management on an outbreak of bovine respiratory disease.

Epidemic curves, odds ratios and chisquare were used to investigate an epidemic of respiratory disease in a pen of feedlot cattle. The cattle were divided into four groups by an eartag number received at processing. Data for each group were collected from feedlot records describing purchase, transportation and processing histories, daily feeding methods, daily pen movements, daily diagnoses, treatment and mortality rates. These data were used to describe the effects of market origin and feeding management on the levels and distribution of respiratory disease.The three groups of cattle purchased from auction markets and started on high levels of grain in their rations were determined to be 6.3 times (P<0.0005) more likely to be treated for any disease, 4.9 times (P<0.0005) more likely to be treated for respiratory disease, 12.7 times (P<0.0025) more likely to die, and 6.7 times (P<0.0471) more likely to die with respiratory disease than the group made up primarily of farm-assembled heifers and started on a 10% grain ration with time for adjustment to grain.

Preventive medicine in the feedlot.

Controlling feedlot disease is not an easy task. Veterinarians and feedlot managers face a very complex problem with continually changing conditions. A management plan should be carefully developed by the veterinarian in consultation with the manager, nutritionist, and other advisors. A management system based on continual disease surveillance, adequate records, and written treatment protocols and preventive plans will greatly assist in reducing death losses in feedlots.

A retrospective survey of diseases of feedlot cattle in Alberta.

A survey of feedlot managers was used to obtain information on disease occurrence, management practices and preventive techniques employed in feedlots in Alberta. Respiratory diseases were reported to be the most frequent causes of sickness and death. Costs associated with disease occurrence were estimated to be C $15.6 million in feedlots in Alberta annually during the period under study.

Preventive medicine and management in beef feedlots.

The objectives of beef feedlot preventive medicine are to reduce morbidity, mortality and culling rates, maximize feed efficiency and optimize expenditures for biologicals and pharmaceuticals. The veterinarian must provide regular inspection of all areas of the feedlot and constantly monitor disease incidence. The provision of advice on vaccination, treatment schedules, necropsies on all dead cattle and the regular analysis of disease and production records are all part of feedlot preventive medicine. All of this is aimed at improving net economical gain for the producer.

Blood levels of sulfamethazine achieved in beef calves on medicated drinking water.

Studies on the use of sodium sulfamethazine in drinking water at three levels (572, 1028 and 1848 mg/L) were conducted in healthy weaned beef calves under similar dietary and environmental conditions. Blood sulfonamide levels greater than 5 mg/dl were attained with each treatment level but at different time intervals. The maximum levels in blood were achieved with the highest concentration in the water. However, a reduction in water intake caused a lower than anticipated dose of sulfamethazine. Under the conditions of the experiment the administration of sulfonamide in drinking water may be an effective means of mass medication of cattle.