A comparative molecular field analysis study of obtusifoliol 14α-methyl demethylase inhibitors

This report describes the development of a Comparative Molecular Field Analysis (CoMFA) model from a set of obtusifoliol 14α-methyl demethylase (DM) inhibitors to aid in the design of herbicides targeting sterol biosynthesis. CoMFA is a three-dimensional (3-D) quantitative structure–activity relationship (QSAR) method that is useful in the probing of receptor binding sites when experimental structure data are unavailable. Conformational analysis and SAR of some rigid and active analogs were used to build the initial model using the active analog hypothesis. The model was subsequently used to design compounds that retain the active site shape requirements, but incorporate physical properties that favor soil-applied herbicidal action. In addition, a second-generation CoMFA model incorporating the newly designed inhibitors was developed and represents the current understanding of the DM binding site. This model was derived from a pharmacophore developed from two methods, the active analog approach as well as from the Catalyst program. The fact that two independent methods produced a similar pharmacophore strengthens the validity of the model. © 1999 Society of Chemical Industry     

Effects of training on potassium homeostasis during exercise and skeletal muscle Na+,K(+)-ATPase concentration in young adult and middle-aged Dutch Warmblood horses

OBJECTIVE: To investigate the effects of moderate short-term training on K+ regulation in plasma and erythrocytes during exercise and on skeletal muscle Na+,K(+)-ATPase concentration in young adult and middle-aged horses. ANIMALS: Four 4- to 6-year-old and four 10- to 16-year-old Dutch Warmblood horses. PROCEDURE: The horses underwent a 6-minute exercise trial before and after 12 days of training. Skeletal muscle Na+,K(+)-ATPase concentration was analyzed in gluteus medius and semitendinosus muscle specimens before and after the 12-day training period. Blood samples were collected before and immediately after the trials and at 3, 5, 7, and 10 minutes after cessation of exercise for assessment of several hematologic variables and analysis of plasma and whole-blood K+ concentrations. RESULTS: After training, Na+,K(+)-ATPase concentration in the gluteus medius, but not semitendinosus, muscle of middle-aged horses increased (32%), compared with pretraining values; this did not affect the degree of hyperkalemia that developed during exercise. The development of hyperkalemia during exercise in young adult horses was blunted (albeit not significantly) without any change in the concentration of Na+,K(+)-ATPase in either of the muscles. After training, the erythrocyte K+ concentration increased (7% to 10%) significantly in both groups of horses but did not change during the exercise trials. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, the activation of skeletal muscle Na+,K(+)-ATPase during exercise is likely to decrease with age. Training appears to result in an increase in Na+,K(+)-ATPase activity in skeletal muscle with subsequent upregulation of Na+,K(+)-ATPase concentration if the existing Na+,K(+)-ATPase capacity cannot meet requirements.     

Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility.     

Effects of Dietary Protein Concentration on Growth, Survival, and Body Composition of Muskellunge Esox musquinongy and Tiger Muskellunge Esox masquinongy × E. luscius Fingerlings

Growth rate, survival and body composition of muskellunge Esox musquinongy (initial mean total length = 125 mm) and tiger muskellunge E. masquinongy × E. lucius (initial mean total length = 115 mm) fed semi-purified diets differing in protein level from 31 to 40% and 34 to 45%, respectively, were evaluated in 8-wk trials. The minimum protein level that yielded satisfactory growth rates for muskellunge was 37%, whereas tiger muskellunge growth rates were highest for fish fed a 45% protein diet. Growth differences were caused by changes in protein quantity, not quality, as amino acid ratios were similar for test diets and showed no imbalances among diets. Condition factors for both fishes increased with dietary protein. Survival of muskellunge (73%) and tiger muskellunge (97%) was not pffected by diet type. Body protein increased and fat content decreased in both fishes when fed higher dietary protein. Results suggest that both fishes respond similarly to dietary changes, but that substantial differences exist in protein requirements.     

NOCTURNAL ACTIVITY OF BIRDS ON SHRIMP MARICULTURE PONDS

Birds can reduce production of shrimp in mariculture grow-out ponds through predation and competition for feed. This study involved weekly nocturnal enumeration of bird populations and observation of nocturnal avian habits on a series of 0.1 ha experimental ponds at the Texas A&M University Shrimp Mariculture Facility at Corpus Christi, Texas. Observations were conducted hourly from sunset to sunrise during October through December 1980. The rate of predation was evaluated every three hours by comparing the number of feeding attempts to the number of successful prey captures over a known time period. Gulls (Family Laridae) acted primarily as competitors for feed. Active feeding by gulls was restricted to daylight hours, consequently feed loss decreased when the feed was distributed at or after dusk. Major preadatory birds included herons and egrets (F. Ardeidae), migratory ducks (F. Anatidae), and, to a lesser extent, grebes (F. Podicipedidae) and shorebirds (Order Charadriiformes). Bird predation decreased pond production by 75% in some ponds.     

Use of a hydroxyapatite orbital implant in a cosmetic corneoscleral prosthesis after enucleation in a horse

A hydroxyapatite orbital implant was used after enucleation of an eye from a 5-year-old performance horse. A custom-made corneoscleral prosthesis was made and fitted over the hydroxyapatite implant. The implant and surgery were well tolerated. Placement of a cosmetic prosthesis is desired after enucleation of equine eyes to allow horses to return to competition. Synthetic spheres consisting of methylmethacrylate or silicone have been used, although reported complications have included extrusion, infection, and poor cosmetic results. Hydroxyapatite orbital implants made from marine coral allow vascular and fibrous tissue growth from the host orbit into the implant, which decreases the possibility of implant extrusion or infection and allows enhanced healing of defects in the overlying conjunctiva. Extraocular muscle fixation onto the implant permits motility and assists in the prevention of implant extrusion.     

Immunogenicity of bovine parainfluenza type 3 virus proteins encapsulated in nanoparticle vaccines,following intranasal administration to mice

Stimulation of long lasting, protective immunity to respiratory viruses is often difficult to achieve with conventional respiratory vaccines. Polymeric nanoparticles, incorporating viral proteins have been shown to offer sustained release of antigen, with consequent prolongued stimulation of the respiratory immune system. In this paper the efficacy of two nanoparticle vaccines (poly-lactide-co-glycolide, PLGA; polymethylmethacrylate, PMMA), incorporating proteins of bovine parainfluenza type 3 virus (BPI-3) was investigated. As a preliminary to experiments in calves, it was considered essential to demonstrate immunogenicity of the experimental vaccine in mice. Mice immunised with PLGA nanoparticles, containing BPI-3 proteins, developed higher levels of virus-specific antibody than mice immunised with the PMMA vaccine or with soluble viral proteins alone. Immunoblotting using serum from the vaccinated mice, demonstrated strong reactions against the major BPI-3 proteins.     

Pulmonary embolism associated with canine total hip replacement

OBJECTIVE: To determine by pulmonary perfusion scans and ultrasonography if embolemia occurs during total hip replacement (THR) surgery in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Forty client-owned dogs that had THR surgery. METHODS: Thoracic radiographs were taken immediately after THR and immediately after completion of (99m)Tc-MAA lung scans. Scintigraphy was performed in 28 dogs, 48 hours after THR. Intraoperative ultrasonography (intercostal or transesophageal) was performed in another 12 dogs that had THR. The right atrium and ventricle and pulmonary outflow tract were observed during and for 5 to 8 minutes after femoral component insertion into medullary canals prepared by reaming, and lavage and aspiration of debris before filling with polymethylmethacrylate in dough stage. A modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) classification system was used to evaluate lung scans. RESULTS: No pulmonary radiographic abnormalities were identified. Segmental and subsegmental perfusion defects occurred in 23 (82%) dogs and were classified as severe in 9 (32%) dogs, moderate in 11, and mild in 3. There was no particular lobe predilection. Patchy mulberry-appearing defects, indicative of fat embolism, were most common. Embolemia was observed by ultrasound in 10 dogs. Variable-sized particles occurred in 8 dogs, particles and bubbles in 2 dogs, and no emboli were observed in 2 dogs. Embolemia was observed within 10 seconds after femoral stem insertion and lasted < 1 minute. Pneumoemboli remained in the right atrium for > 8 minutes before dislodgement. CONCLUSIONS: Embolemia of either air, particles, or both occurs in most dogs during THR surgery. CLINICAL RELEVANCE: Most dogs seemingly spontaneously recover from pulmonary embolism that occurs during THR. The risk of clinical complications from this pulmonary embolism should be taken seriously, even though the exact morbidity and mortality rates are unknown.     

Canine choroidal melanoma with metastases

A 3-year-old-female, spayed Golden Retriever was examined for a unilateral retinal detachment with exophthalmos. Ultrasonographically, a mass was detected with intra- and extraocular extension. The orbit was exenterated and the dog recovered uneventfully. Histopathologic diagnosis was a primary choroidal melanoma with orbital extension, however, the behavioral and cytologic features were benign. Routine examinations postsurgically were nonremarkable. Twenty-one months after surgery the dog was euthanized for respiratory collapse with radiographic signs of metastasis. Necropsy revealed black lesions in the lung and liver. Histopathologic diagnosis was metastatic melanoma with morphology and behavior identical to the primary choroidal melanoma. This is the first definitive case of a canine choroidal melanoma with metastasis.