Use of bone morphogenetic proteins for augmentation of bone regeneration

A large body of preclinical and clinical data now documents that recombinant BMPs can be used for skeletal regeneration in humans and animals. Recombinant human BMP-2 and BMP-7 have been approved for use in human patients with long-bone fractures and nonunions and in patients undergoing lumbar fusion or various maxillofacial and dental regenerative procedures. These products have also been made available for veterinary use.     

Structure-activity relationships of triazinone herbicides on resistant weeds and resistant Chlamydomonas reinhardtii

Weeds resistant to the s-triazine herbicide atrazine also show resistance to the triazinone herbicide metribuzin. However, with highly lipophilic triazinones, thylakoids isolated from atrazine-resistant Amaranthus retroflexus (mutation at position Ser₂₆₄ of the photosystem II D-1 reaction centre protein) in general show a higher pI₅₀ value in photosystem II electron transport than those from the wild type (i.e. negative cross-resistance; ‘supersensitivity’). A quantitative structure–activity relationship (QSAR) can be established, wherein the lipophilicity of the compound plays a major role. In in-vivo experiments, it was found that the triazinone DRW2698 killed resistant Amaranthus retroflexus and Chenopodium album whereas the wild type was almost unaffected. Triazinones were further investigated in five different mutants of Chlamydomonas rheinhardtii (mutations in the D-1 protein at positions Ser₂₆₄, Ala₂₅₁, Leu₂₇₅, Phe₂₅₅, and Val²¹⁹). Inhibitory activity of all triazinones was generally enhanced in the Phe₂₅₅ mutant but decreased in the Val₂₁₉ mutant. In the other mutants, biological activity was decreased when position 3 of the triazinone was substituted by CH₃, OCH₃, SCH₃, NHCH₃ or N(CH₃)₂. However, negative cross-resistance was again observed when this position was occupied by free thiol. It is therefore suggested that these two groups of triazinones orient themselves differently within the herbicide binding niche of the photosystem II D-1 protein.     

Porphyric insecticides. IV: Structure-activity study of substituted phenanthrolines

The porphyric-insecticide-modulating activities of 1,10-phenanthroline and eight of its analogs were investigated. The insecticidal efficacy of these compounds was closely associated with their ability to enhance the conversion of exogenous δ-aminolevulinic acid (ALA) to protoporphyrin IX (Proto). As observed for photodynamic herbicidal effects in plants, the presence of nitrogen atoms at positions 1 and 10 of the macrocycle was essential for porphyric insecticidal activity. This was evidenced by the very limited activity of phenanthrene, in which positions 1 and 10 are occupied by carbon instead of nitrogen atoms. On the other hand, enhancement of Proto formation and porphyric insecticidal activity were maintained following methyl, chloro and nitro group substitution at the periphery of 1,10-phenanthroline. In contrast, Proto levels and photodynamic toxicity were reduced by hydroxy and phenyl substitution at the same positions. Benzyl substitution at the 2–3 and 8–9 positions was also inhibitory. Quantitative structure-activity calculations suggested a relationship between peripheral group substitution and physicochemical properties of the substituted compounds. Electron density changes in 1,10-phenanthroline and its analogs that appeared to be related to reduced efficacy included (a) appearance of positive charge-binding volumes at positions 4 and 7 of the 1,10-phenanthroline macrocycle, which flanks positive charge-repelling volumes, (b) a dramatic increase in superdelocalisability (i.e. electron density) over some unoccupied molecular orbitals, and (c) electronic charge at positions 1 and 10 of the macrocycle. Large increases in van der Waals volumes also exerted negative effects on insecticidal efficacy.     

Usefulness, completeness, and accuracy of Web sites providing information on osteoarthritis in dogs

OBJECTIVE: To evaluate the quality of information regarding osteoarthritis (OA) in dogs currently available on the World Wide Web. DESIGN: Survey study. PROCEDURE: 5 search engines were searched with the keywords "dog," "degenerative joint disease," "canine," and "osteoarthritis," and the first 50 sites listed by each search engine were analyzed. Unique Web site addresses were distributed to 3 diplomates of the American College of Veterinary Surgeons, who provided a standardized evaluation of each site. RESULTS: 30 unique Web sites were evaluated. Twenty (66%) provided information consistent with conventional knowledge as outlined in textbooks and peer-reviewed literature, 8 (27%) provided experimental or anecdotal information in addition to conventional knowledge, and 2 (7%) provided misleading information. Mean scores for overall usefulness of the information provided in regard to clinical features of and treatment for OA were 1.3 and 1.5, respectively (1 = information of minimal use; 5 = very useful information). Twenty-three (77%) sites encouraged pet owners to seek the advice of a veterinarian. Twenty-three (77%) sites were given overall quality scores < 2, and 7 (23%) were given scores between 2 and 3 (1 = site was counterproductive; 5 = site was very valuable). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the quality of information currently available on the Web that addresses OA in dogs is questionable. Although most of the sites conveyed some conventional information with reasonable accuracy, the information was incomplete, of minimal use, and often considered counterproductive.     

Effects of storage time and temperature on pH,specific gravity,and crystal formation in urine samples from dogs and cats

OBJECTIVE: To determine effects of storage temperature and time on pH and specific gravity of and number and size of crystals in urine samples from dogs and cats. DESIGN: Randomized complete block design. ANIMALS: 31 dogs and 8 cats. PROCEDURE: Aliquots of each urine sample were analyzed within 60 minutes of collection or after storage at room or refrigeration temperatures (20 vs 6 degrees C [68 vs 43 degrees F]) for 6 or 24 hours. RESULTS: Crystals formed in samples from 11 of 39 (28%) animals. Calcium oxalate (CaOx) crystals formed in vitro in samples from 1 cat and 8 dogs. Magnesium ammonium phosphate (MAP) crystals formed in vitro in samples from 2 dogs. Compared with aliquots stored at room temperature, refrigeration increased the number and size of crystals that formed in vitro; however, the increase in number and size of MAP crystals in stored urine samples was not significant. Increased storage time and decreased storage temperature were associated with a significant increase in number of CaOx crystals formed. Greater numbers of crystals formed in urine aliquots stored for 24 hours than in aliquots stored for 6 hours. Storage time and temperature did not have a significant effect on pH or specific gravity. CONCLUSIONS AND CLINICAL RELEVANCE: Urine samples should be analyzed within 60 minutes of collection to minimize temperature- and time-dependent effects on in vitro crystal formation. Presence of crystals observed in stored samples should be validated by reevaluation of fresh urine.     

Associations between dry dietary factors and canine calcium oxalate uroliths

OBJECTIVE: To identify factors in dry diets associated with the occurrence of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 600 dogs with CaOx uroliths and 898 dogs without urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Compared with diets with the highest concentrations of sodium, dry diets with the lowest concentrations of sodium, phosphorus, calcium, chloride, protein, magnesium, or potassium were linearly associated with increased risk of CaOx urolith formation. Significant nonlinear associations between increased occurrence of CaOx uroliths and urine acidifying potential and low moisture content were observed. Significant nonlinear associations between decreased occurrence of CaOx uroliths and carbohydrate and fiber contents were observed. A significant association between the occurrence of CaOx uroliths and dietary fat was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dry diets formulated to contain high concentrations of protein, calcium, phosphorus, magnesium, sodium, potassium, and chloride may minimize formation of CaOx uroliths. In addition, comparison of risk and protective factors of various diet ingredients fed to dogs with CaOx uroliths suggests that although similar findings were observed in canned and dry formulations, in general, greater risk is associated with dry formulations. However, before these hypotheses about dietary modifications are adopted by food manufacturers, they must be investigated by use of appropriately designed clinical studies of dogs with CaOx urolithiasis.     

Associations between dietary factors in canned food and formation of calcium oxalate uroliths in dogs

OBJECTIVE: To identify dietary factors in commercially available canned foods associated with the development of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 117 dogs with CaOx uroliths and 174 dogs without urinary tract disease. PROCEDURE: Case dogs were those that developed CaOx uroliths submitted to the Minnesota Urolith Center for quantitative analysis between 1990 and 1992 while fed a commercially available canned diet. Control dogs were those without urinary tract disease evaluated at the same veterinary hospital just prior to or immediately after each case dog. A content-validated multiple-choice questionnaire was mailed to each owner of case and control dogs with the permission of the primary care veterinarian. Univariate and multivariate logistic regressions for each dietary component were performed to test the hypothesis that a given factor was associated with CaOx urolith formation. RESULTS: Canned foods with the highest amount of protein, fat, calcium, phosphorus, magnesium, sodium, potassium, chloride, or moisture were associated with a decreased risk of CaOx urolith formation, compared with diets with the lowest amounts. In contrast, canned diets with the highest amount of carbohydrate were associated with an increased risk of CaOx urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE: Feeding canned diets formulated to contain high amounts of protein, fat, calcium, phosphorus, magnesium, sodium, potassium, chloride, and moisture and a low amount of carbohydrate may minimize the risk of CaOx urolith formation in dogs.     

The effects of femur and implant position on the radiographic assessment of total hip femoral implants in dogs

OBJECTIVE: To determine the effect of femur positioning and femoral implant placement on the radiographic assessment of total hip femoral implants in dogs. STUDY DESIGN: Cadaveric study. ANIMALS: Five canine femurs. METHODS: Five canine femurs were fitted with total hip implants, in predetermined locations, postmortem. Each femur was moved through a defined range of motion and radiographed at specific intervals. Radiographs were then digitized, and implant position was measured using previously described methods. Regression analysis was conducted to determine whether varied femoral position resulted in a consistent (linear) pattern of change in the value of each particular measurement. RESULTS: Change in the position of the femur relative to the film cassette caused significant variation in the perceived position of the implant. The placement of the implant within the femur determined which measurements were affected and to what degree. CONCLUSIONS: The information obtained from standard clinical radiographs and conventional methods of quantitative analysis does not consistently provide an accurate assessment of the placement of the femoral implant within the femoral canal. Such data cannot be used to correlate implant position with implant failure.     

Quantifying the nitrogen retention capacity of natural wetlands in the large-scale drainage basin of the Baltic Sea

We estimate the nitrogen retention capacity of natural wetlands in the 1.7 million km² Baltic Sea drainage basin, using a wetland GIS data base. There are approximately 138,000 km² of wetlands (bogs and fens) in the Baltic Sea drainage basin, corresponding to 8% of the area. The input of nitrogen to natural wetlands from atmospheric deposition was estimated to 55,000–161,000 ton y¹. A map of the deposition of both wet and dry nitrogen is presented. The input from the human population was estimated to 255,000 ton y¹ in terms of excretory release in processed sewage water. There may also be leakage from forests and agricultural land into the wetlands. Due to lack of data on hydrology and topography, such potential nitrogen sources are not accounted for here. The capacity of the wetlands to retain the atmospheric deposition of nitrogen was estimated to 34,000–99,000 ton y¹. The potential retention by wetlands was estimated to 57,000–145,000 ton y¹ when the nitrogen input from the human population was added. If drained wetlands were to be restored and their area added to the present wetland area, the nitrogen retention capacity was estimated to increase to 196,000–261,000 ton y¹. Our results indicate that existing natural wetlands in the Baltic Sea drainage basin annually can retain an amount of nitrogen which corresponds to about 5–13% of annual total (natural and anthropogenic) nitrogen emissions entering the Baltic Sea. The ecosystem retention service performed by wetlands accounts for a substantial nitrogen removal, thereby reducing the eutrophication of the Baltic Sea.